A controlled thermoalgesic stimulation device to identify novel pain perception biomarkers

Objective To develop a new device that will help identify physiological markers of pain perception by reading the brain’s electrical activity and the bodies hemodynamic interactions while applying thermoalgesic stimulation. Methods: We designed a compact prototype that generates well-controlled thermal stimuli using a computer driven Peltier cell while simultaneously capturing electroencephalography (EEG) and photoplethysmography (PPG) signals as the stimuli are varied. The study was performed on 35 healthy subjects (mean age 30.46 years, SD 4.93 years; 20 males, 15 females) and to account for the inter-subject variability in the tolerance to thermal pain, we first determined the heat pain threshold (HPT) for each subject, defined as the maximum temperature that the subject can withstand when the Peltier cell gradually increases the temperature. Subsequently, we defined the pain parameters associated with a stimulation temperature equivalent to 90% of the HPT, comparing this to the no-pain state (control) in the absence of thermoalgesic stimulation. Results: Both the one-dimensional and the two-dimensional spectral entropy (SE) obtained from both the EEG and PPG signals could differentiate the condition of pain. In particular, the PPG SE was significantly reduced in association with pain, while the SE for EEG increased slightly. Moreover, significant discrimination occurred within a specific range of frequencies, 26-30 Hz for EEG and about 5-10 Hz for PPG. Conclusion: Hemodynamics, brain dynamics and their interactions can discriminate thermal pain perception. Significance: The possibility of monitoring on-line variations in thermal pain perception using a similar device and algorithms may be of interest to study different pathologies that affect the peripheral nervous system, such as small fiber neuropathies, fibromyalgia or painful diabetic neuropathy.